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Scientists find genes that may cause inflammatory bowel disease

Using genetic "fine-mapping," researchers have zoomed in on just a few genetic variants that may trigger the autoimmune condition inflammatory bowel disease.

Researchers have narrowed down a few genetic variants that may cause inflammatory bowel disease.

Inflammatory bowel disease (IBD) affects between 1 and 1.3 million people in the United States, according to the Centers for Disease Control and Prevention (CDC). The condition can be debilitating, as the body's own immune system does not recognize parts of its digestive tract and attacks them.

It is not currently known what causes IBD, nor is there a cure for the condition. But new research brings us closer to understanding this disease, as some of the genetic underpinnings for IBD are revealed.

Researchers from the Wellcome Trust Sanger Institute in Hinxton in the United Kingdom teamed up with scientists from the Broad Institute of MIT and Harvard University, both in Cambridge, MA, as well as the GIGA Institute of the University of Liège in Belgium, to find out which genetic variations are behind the condition.

The findings were published in the journal Nature, and the first author of the study is Dr. Hailiang Huang, from the Massachusetts General Hospital and the Broad Institute of MIT.

Studying the genetic variants behind IBD

Dr. Huang and colleagues performed a genome-wide association study (GWAS) of 67,852 people. A GWAS is a method that quickly scans for biomarkers across whole sets of DNA, or genomes, of a large number of people in order to find genetic associations with a particular disease.

As the authors of the new study report, previous studies have found 200 genetic loci associated with the illness, but it was not entirely clear precisely which variants were involved in the disease.

Dr. Huang explains further, saying, "An issue with studying complex diseases is that it can be hard to move from genetic associations, usually including many genetic variants of similar evidence, to knowing exactly which variants are involved."

"We need to be careful in deciding when we are sure we have the right variant. This new technique helps us to pinpoint which genetic variants are implicated in IBD with greater confidence."

In the new research, Dr. Huang and team used "high-density genotyping" and applied three statistical analyses. As a result, they found 94 genetic locations.

Of these, the team identified a further 18 locations that they could associate with a single genetic variant, with a degree of certainty of over 95 percent.

Additionally, they found 27 associations to a single genetic variant with over 50 percent accuracy.

'Zooming in on the genetic culprits'

This procedure of "fine-mapping" allowed the researchers to see which genes are involved in the condition and which are not, by separating these genetic variants from others that were closely located in the genome.

Furthermore, the authors note that the fine-mapping of large population samples can turn genetic associations into "statistically convincing causal variants."

"We have taken the biggest ever data set for IBD and applied careful statistics to narrow down to the individual genetic variants involved. Now we have a clearer picture of which genes do and do not play a role in the disease. We are zooming in on the genetic culprits of IBD."

Co-lead author Dr. Jeffrey Barrett, Wellcome Trust Sanger Institute

Co-lead author Prof. Michel Georges, from the GIGA Institute of the University of Liège, also weighs in, saying, "These results will help towards rational drug discovery for complex human diseases like IBD, and possibly for the development of personalized medicine by finding biomarkers for more effective prescription of existing drugs."

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